Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A.

ABSTRACT:

Background

Monogenic defects of synaptic vesicle (SV) homeostasis have been implicated in many neurologic diseases, including autism, epilepsy, and movement disorders. In addition, abnormal vesicle exocytosis has been associated with several endocrine dysfunctions.

Methods

We report an 11 year old girl with learning disabilities, tremors, ataxia, transient hyperglycemia, and muscle fatigability responsive to albuterol sulfate. Failure of neuromuscular transmission was confirmed by single fiber electromyography. Electron microscopy of motor nerve terminals revealed marked reduction in SV density, double-membrane-bound sacs containing SVs, abundant endosomes, and degenerative lamellar bodies. The patient underwent whole exome sequencing (WES) and relevant sequence variants wer

SUBMITTER: Maselli RA 

PROVIDER: S-EPMC6014458 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature